1. Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease
- Author
-
Ping Xu, Marta Paez-Ribes, Shan Man, Robert S. Kerbel, Annabelle Chow, Kabir A. Khan, Janna Krüger, Florence T. H. Wu, and Elizabeth Pham
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,medicine.medical_treatment ,Cancer immunotherapy ,Article ,Metastasis ,03 medical and health sciences ,Targeted therapies ,0302 clinical medicine ,Breast cancer ,Renal cell carcinoma ,Internal medicine ,medicine ,Adjuvant therapy ,Neoadjuvant therapy ,Chemotherapy ,business.industry ,Sunitinib ,Cancer ,medicine.disease ,female genital diseases and pregnancy complications ,3. Good health ,030220 oncology & carcinogenesis ,Tumour immunology ,business ,Tumour angiogenesis ,medicine.drug - Abstract
Background There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. Methods This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously develop after surgical resection of primary kidney or breast tumours derived from orthotopic implantation of murine cancer cell lines (RENCAluc or EMT-6/CDDP, respectively). Results In the RENCAluc model, adjuvant sunitinib plus anti-PD-L1 improved overall survival compared to either drug alone, while the same combination was ineffective as early therapy for unresected primary tumours or late-stage therapy for advanced metastatic disease. In the EMT-6/CDDP model, anti-PD-L1 was highly effective as an adjuvant monotherapy, while its combination with paclitaxel chemotherapy (with or without anti-VEGF) was most effective as a neoadjuvant therapy. Conclusions Our preclinical data suggest that anti-PD-L1 plus sunitinib may warrant further investigation as an adjuvant therapy for RCC, while anti-PD-L1 may be improved by combining with chemotherapy in the neoadjuvant but not the adjuvant setting of treating breast cancer.
- Published
- 2018